Q&A: IL-18 Serum Levels and Cardiovascular Risk in Psoriatic Arthritis, Ankylosing Spondylitis

Patients with peripheral psoriatic arthritis (PsA) have a more a pronounced proinflammatory and cardiovascular risk profile than patients with axial PsA or ankylosing spondylitis, according to a study published in the Journal of Clinical Medicine.¹ Moreover, in patients with PsA, but not in those with ankylosing spondylitis, interleukin-18 (IL-18) is associated with higher disease activity and proatherogenic lipid profile, leading to increased cardiovascular risk.

In this Q&A, corresponding author Krzysztof Bonek, MD, PhD, professor of medicine at the National Institute of Geriatrics, Rheumatology and Rehabilitation in Warsaw, Poland, discussed the research and its findings.

The study included 94 patients with ankylosing spondylitis and 61 patients with PsA. Patients with PsA and peripheral joint involvement had the highest IL-18 serum levels, at 160 pg/mL, compared with 116 pg/mL for those with axial PsA and 80 pg/mL for patients with ankylosing spondylitis. In patients with PsA and in a subgroup of patients with PsA and ischemic heart disease, IL-18 positively correlated with atherogenic index and triglycerides serum concentrations, while negatively with high-density cholesterol (HDL) levels. In those with PsA plus ischemic heart disease, IL-18 serum levels correlated positively with the Disease Activity Index for Psoriatic Arthritis (DAPSA).

Rheumatology Network: Why was the study conducted?

Krzysztof Bonek, MD, PhD: Our previous studies have shown an increased incidence of coronary atherosclerosis in patients with ankylosing spondylitis and PsA. Interestingly, we found that patients with PsA have a more pro-atherogenic lipid profile thanpatients with ankylosing spondylitis and a general "healthy" population, which we believe may suggest a different or additional pathomechanism leading to an increased risk of cardiovascular diseases in PsA. Further, in search of PsA dedicated proinflammatory mediators, we assumed IL-18 might have a unique role since IL-18 gene expression has been found in psoriatic plaques, osteoblasts, synovial fluid and atherosclerotic plaques.

RN: What were the surprises from the findings?

KB: Patients with psoriasis and peripheral joint inflammation had higher serum levels of IL-18 and were characterized by a more pronounced proinflammatory,proatherogenic and cardiovascular risk profile than patients with the axial PsA or ankylosing spondylitis.

RN: How significant are the findings?

KB: This is the first study to show that differences in serum lipid profile and cardiovascular risk between ankylosing spondylitis and different phenotypes of PsA may be related to the multidirectional action of IL-18 in PsA.

In the future, the potential use of IL-18 inhibitors could be a promising new direction in the treatment of patients with PsA and high cardiovascular risk. However, further studies are required.

RN: What is the current practice and how could the results possibly change things?

KB: PsA and ankylosing spondylitis are recognized as conditionsassociated with increased cardiovascular risk. However, our studies indicate that the cardiovascular risk in patients with PsA, especially in the group of patients with peripheral arthritis, is underestimated.

In addition, in PsA, but not in ankylosing spondylitis, the tendency to develop obesity andhypertriglyceridemia appears to be related to disease activity and IL-18 levels. Therefore, treatment should be focused on achieving clinical remission and modifiable cardiovascular risk factors.

RN: What are the takeaway points for clinicians?

KB:PsA, but the predominantly peripheral form of PsA, is oftenassociated with the development of dyslipidemia, obesity and increased cardiovascular risk.

In the course of ankylosing spondylitis, the pathomechanism leading to an increased riskof cardiovascular complications is different. It does not seem to be associated with dyslipidemia and the involvement of IL-18.

RN: Is there anything else you would like to add?

KB: As current cardiovascular risk assessment methods are maladjusted in systemic rheumatic diseases, physicians should be proactive in searching for modifiable cardiovascular risk factors and actively search for atherosclerotic plaques.

Reference:

Bonek K, Kuca-Warnawin E, Kornatka A, Zielińska A, Wisłowska M, Kontny E, Głuszko P. Associations of IL-18 with Altered Cardiovascular Risk Profile in Psoriatic Arthritis and Ankylosing Spondylitis. Journal of Clinical Medicine. 2022; 11(3):766. https://doi.org/10.3390/jcm11030766